Plasma taurine level is linked to symptom burden and clinical outcomes in post-COVID condition.

BACKGROUND: A subset of individuals (10-20%) experience post-COVID condition (PCC) subsequent to initial SARS-CoV-2 infection, which lacks effective treatment. PCC carries a substantial global burden associated with negative economic and health impacts. This study aims to evaluate the association between plasma taurine levels with self-reported symptoms and adverse clinical outcomes in patients with PCC. METHODS AND FINDINGS: We analyzed the plasma proteome and metabolome of 117 individuals during their acute COVID-19 hospitalization and at the convalescence phase six-month post infection. Findings were compared with 28 age and sex-matched healthy controls. Plasma taurine levels were negatively associated with PCC symptoms and correlated with markers of inflammation, tryptophan metabolism, and gut dysbiosis. Stratifying patients based on the trajectories of plasma taurine levels during six-month follow-up revealed a significant association with adverse clinical events. Increase in taurine levels during the transition to convalescence were associated with a reduction in adverse events independent of comorbidities and acute COVID-19 severity. In a multivariate analysis, increased plasma taurine level between acute and convalescence phase was associated with marked protection from adverse clinical events with a hazard ratio of 0.13 (95% CI: 0.05-0.35; p<0.001). CONCLUSIONS: Taurine emerges as a promising predictive biomarker and potential therapeutic target in PCC. Taurine supplementation has already demonstrated clinical benefits in various diseases and warrants exploration in large-scale clinical trials for alleviating PCC.

Taurine Improved Autism-Like Behaviours and Defective Neurogenesis of the Hippocampus in BTBR Mice through the PTEN/mTOR/AKT Signalling Pathway.

Effective treatment of patients with autism spectrum disorder (ASD) is still absent so far. Taurine exhibits therapeutic effects towards the autism-like behaviour in ASD model animals. Here, we determined the mechanism of taurine effect on hippocampal neurogenesis in genetically inbred BTBR T+ tf/J (BTBR) mice, a proposed model of ASD. In this ASD mouse model, we explored the effect of oral taurine supplementation on ASD-like behaviours in an open field test, elevated plus maze, marble burying test, self-grooming test, and three-chamber test. The mice were divided into four groups of normal controls (WT) and models (BTBR), who did or did not receive 6-week taurine supplementation in water (WT, WT+ Taurine, BTBR, and BTBR+Taurine). Neurogenesis-related effects were determined by Ki67 immunofluorescence staining. Western blot analysis was performed to detect the expression of phosphatase and tensin homologue deleted from chromosome 10 (PTEN)/mTOR/AKT pathway-associated proteins. Our results showed that taurine improved the autism-like behaviour, increased the proliferation of hippocampal cells, promoted PTEN expression, and reduced phosphorylation of mTOR and AKT in hippocampal tissue of the BTBR mice. In conclusion, taurine reduced the autism-like behaviour in partially inherited autism model mice, which may be associa-ted with improving the defective neural precursor cell proliferation and enhancing the PTEN-associated pathway in hippocampal tissue.

Study of correlations between serum taurine, thyroid hormones and echocardiographic parameters of systolic function in clinically healthy Golden retrievers fed with commercial diet.

Taurine deficiency predisposes to the development of nutritional dilated cardiomyopathy and is widespread in dogs fed with non-traditional diets. However, Golden retrievers show lower plasma taurine concentration and an impaired systolic function compared to breeds of the same size and morphotype. For these reasons, it can be difficult to classify a subject from a cardiological point of view, with the risk of considering as pathological characteristics that can be completely normal in this breed. This is a cross-sectional multicenter study. The aims were 1) to identify breed-specific range of serum taurine concentration, 2) to describe a correlation between serum taurine concentration and echocardiographic parameters of systolic function in clinically healthy Golden retrievers fed with traditional diet, 3) to identify a correlation between thyroid hormones, serum taurine concentration and echocardiographic indices. Sixty clinically healthy Golden retrievers (33% males, 67% females) were included. Fifty-three dogs were fed with traditional diets and their range of serum taurine concentration was 398.2 (31.8-430) nmol/ml. Serum taurine concentration was found to be negatively correlated to systolic internal diameter of the left ventricle and systolic and diastolic left ventricular indices and volumes obtained with different methods, whereas was positively correlated to the left ventricle ejection and shortening fractions but difference was not statistically significative. A weak but significant correlation between serum taurine and T4 was demonstrated. Serum taurine median values in dogs with normal systolic function were higher than in dogs with impaired systolic function. A cut-off of serum taurine concentration of 140.6 nmol/ml had a moderate sensitivity and specificity in the identification of an impaired left ventricular systolic function (AUC 0.6, Se 78%, Sp 44%). This study showed that the median serum taurine concentration was significantly lower in dogs with impaired systolic function. Therefore, echocardiographic monitoring is recommended in all dogs with serum taurine concentration lower than 140.6 nmol/ml.

Influence of taurine on the zootechnical performance and health parameters of juvenile Nile tilapia in a recirculating aquaculture system.

Taurine is considered a conditionally essential amino acid for fish, so its supplementation may improve feed conversion. This study evaluated the supplementation of taurine on growth performance, hematological and immunological parameters, production costs, and survival of Nile tilapia (Oreochromis niloticus) juveniles raised in a recirculating aquaculture system (RAS). A control diet was formulated with 360 g kg-1 of crude protein without fish meal and without taurine supplementation (Control). From the control diet, another diet supplemented with 9.7 g of taurine per kg of feed (Taurine) was produced. Fish fed diet supplemented with taurine had lower daily average weight gain and final average weight compared to the control diet (p < 0.05). It was observed that taurine had no influence on condition factor, survival, or hemato-immunological parameters of Nile tilapia juveniles, but there was a higher mean corpuscular volume and greater nitrogen retention in fish from the control group (p < 0.05). It is concluded that Nile tilapia juveniles do not benefit from taurine supplementation in RAS, even when fed diet containing plant-based protein sources.

Efficacy of taurine-enhanced enteral nutrition in improving the outcomes of critically ill patients: A systematic review and meta-analysis.

BACKGROUND: Taurine is considered an immunomodulatory agent. From current reports on clinical studies, we conducted a systematic review and meta-analysis to investigate the effects of taurine-enhanced enteral nutrition (EN) on the outcomes of critically ill patients to resolve conflicting evidence in literature. METHODS: Literature from PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, SINOMED, and WanFang databases were retrieved, and randomized controlled trials (RCTs) were identified. The time range spanned from January 1, 2000, to January 31, 2024. The Cochrane Collaboration Tool was used to evaluate the risk of bias. We used the GRADE approach to rate the quality of evidence and the I2 test to assess the statistical heterogeneity of the results. Risk ratio (RR), mean difference (MD), and 95% confidence interval (95% CI) were used to analyze measurement data. RESULTS: Four trials involving 236 patients were finally included. The meta-analysis results indicated that taurine-enhanced EN did not reduce mortality (RR = 0.70, p = 0.45, 95% CI [0.28, 1.80], two trials, 176 participants, low quality). There was also no significant difference in length of stay in the intensive care unit (ICU) between the taurine-enhanced EN and control groups. Taurine-enhanced EN may reduce pro-inflammatory factor interleukin-6 (IL-6) levels in critically ill patients（the result about IL-6 cannot be pooled）. However, taurine-enhanced EN had no significant impact on high-sensitivity-C-reactive protein levels (MD = -0.41, p = 0.40, 95% CI [-1.35, 0.54], two trials, 60 participants, low quality). DISCUSSION: Taurine-enhanced EN may reduce IL-6 levels and is not associated with improved clinical outcomes in critically ill patients, which may have potential immunoregulatory effects in critically ill patients. Given that published studies have small samples, the above conclusions need to be verified by more rigorously designed large-sample clinical trials.

A taurine-based hydrogel with the neuroprotective effect and the ability to promote neural stem cell proliferation.

Ischemic stroke, a cerebrovascular disease caused by arterial occlusion in the brain, can lead to brain impairment and even death. Stem cell therapies have shown positive advantages to treat ischemic stroke because of their extended time window, but the cell viability is poor when transplanted into the brain directly. Therefore, a new hydrogel GelMA-T was developed by introducing taurine on GelMA to transplant neural stem cells. The GelMA-T displayed the desired photocuring ability, micropore structure, and cytocompatibility. Its compressive modulus was more similar to neural tissue compared to that of GelMA. The GelMA-T could protect SH-SY5Y cells from injury induced by OGD/R. Furthermore, the NE-4C cells showed better proliferation performance in GelMA-T than that in GelMA during both 2D and 3D cultures. All results demonstrate that GelMA-T possesses a neuroprotective effect for ischemia/reperfusion injury against ischemic stroke and plays a positive role in promoting NSC proliferation. The novel hydrogel is anticipated to function as cell vehicles for the transplantation of neural stem cells into the stroke cavity, aiming to treat ischemic stroke.

Curcumin, Piperine and Taurine Combination Enhances the Efficacy of Transarterial Chemoembolization Therapy in patients with Intermediate Stage Hepatocellular Carcinoma: A Pilot Study.

INTRODUCTION: Diagnosis of the majority of hepatocellular carcinoma (HCC) patients occurs at intermediate to advanced stages, with a few curative therapeutic options being available. It is therefore strongly urgent to discover additional adjuvant therapy for this lethal malignancy. This study aimed to assess the effectiveness of curcumin (C), piperine (P) and taurine (T) combination as adjuvant agents on serum levels of IFN-γ, immunophenotypic and molecular characterization of mononuclear leukocytes (MNLs) in HCC patients treated with Transarterial chemoembolization (TACE). PATIENTS AND METHODS: Serum and MNLs were collected from 20 TACE-treated HCC patients before (baseline-control samples) and after treatment with 5 g curcumin capsules , 10 mg piperine and 0.5 mg taurine taken daily for three consecutive months. Immunophenotypic and molecular characterization of MNLs were determined by flow cytometry and quantitative real time PCR, respectively. In addition, serum IFN-γ level was quantified by ELISA. RESULTS: After receiving treatment with CPT combination, there was a highly significant increase in IFN- γ levels in the sera of patients when compared to basal line control samples. Additionally, the group receiving combined therapy demonstrated a downregulation in the expression levels of PD-1, in MNLs as compared to controls. MNLs' immunophenotyping revealed a significant decline in CD4+CD25+cells (regulatory T lymphocytes). Furthermore, clinicopathological characteristics revealed a highly significant impact of CPT combination on aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alpha feto protein (AFP) levels. CONCLUSION: This study introduces a promising adjuvant CPT combined treatment as natural agents to enhance the management of HCC patients who are candidates to TACE treatment.

Taurine reduces the risk for metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of interconnected risk factors that significantly increase the likelihood of cardiovascular disease and type 2 diabetes. Taurine has emerged as a potential therapeutic agent for MetS. This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of taurine supplementation on MetS-related parameters. METHODS: We conducted electronic searches through databases like Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, encompassing publications up to December 1, 2023. Our analysis focused on established MetS diagnostic criteria, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). Meta-regression explored potential dose-dependent relationships based on the total taurine dose administered during the treatment period. We also assessed secondary outcomes like body composition, lipid profile, and glycemic control. RESULTS: Our analysis included 1024 participants from 25 RCTs. The daily dosage of taurine in the studies ranged from 0.5 g/day to 6 g/day, with follow-up periods varying between 5 and 365 days. Compared to control groups, taurine supplementation demonstrated statistically significant reductions in SBP (weighted mean difference [WMD] = -3.999 mmHg, 95% confidence interval [CI] = -7.293 to -0.706, p = 0.017), DBP (WMD = -1.509 mmHg, 95% CI = -2.479 to -0.539, p = 0.002), FBG (WMD: -5.882 mg/dL, 95% CI: -10.747 to -1.018, p = 0.018), TG (WMD: -18.315 mg/dL, 95% CI: -25.628 to -11.002, p < 0.001), but not in HDL-C (WMD: 0.644 mg/dl, 95% CI: -0.244 to 1.532, p = 0.155). Meta-regression analysis revealed a dose-dependent reduction in DBP (coefficient = -0.0108 mmHg per g, p = 0.0297) and FBG (coefficient = -0.0445 mg/dL per g, p = 0.0273). No significant adverse effects were observed compared to the control group. CONCLUSION: Taurine supplementation exhibits positive effects on multiple MetS-related factors, making it a potential dietary addition for individuals at risk of or already experiencing MetS. Future research may explore dose-optimization strategies and potential long-term benefits of taurine for MetS management.

Taurine Alleviates Experimental Colitis by Enhancing Intestinal Barrier Function and Inhibiting Inflammatory Response through TLR4/NF-κB Signaling.

Taurine (Tau) is a semiessential amino acid in mammals with preventive and therapeutic effects on several intestinal disorders. However, the exact function of taurine in ulcerative colitis (UC) is still largely unclear. In this study, we used two taurine-deficient mouse models (CSAD-/- and TauT-/- mice) to explore the influence of taurine on the progression of UC in both dextran sulfate sodium (DSS)-induced colitis and LPS-stimulated Caco-2 cells. We found that cysteine sulfinic acid decarboxylase (CSAD) and taurine transporter (TauT) expressions and taurine levels were markedly reduced in colonic tissues of mice treated with DSS. The CSAD and TauT knockouts exacerbated DSS-induced clinical symptoms and pathological damage and aggravated the intestinal barrier dysfunction and the colonic mucosal inflammatory response. Conversely, taurine pretreatment enhanced the intestinal barrier functions by increasing goblet cells and upregulating tight junction protein expression. Importantly, taurine bound with TLR4 and inhibited the TLR4/NF-κB pathway, ultimately reducing proinflammatory factors (TNF-α and IL-6) and oxidative stress. Our findings highlight the essential role of taurine in maintaining the intestinal barrier integrity and inhibiting intestinal inflammation, indicating that taurine is a promising supplement for colitis treatment.

Combination of Tramiprosate, Curcumin, and SP600125 Reduces the Neuropathological Phenotype in Familial Alzheimer Disease PSEN1 I416T Cholinergic-like Neurons.

Familial Alzheimer's disease (FAD) is a complex and multifactorial neurodegenerative disorder for which no curative therapies are yet available. Indeed, no single medication or intervention has proven fully effective thus far. Therefore, the combination of multitarget agents has been appealing as a potential therapeutic approach against FAD. Here, we investigated the potential of combining tramiprosate (TM), curcumin (CU), and the JNK inhibitor SP600125 (SP) as a treatment for FAD. The study analyzed the individual and combined effects of these two natural agents and this pharmacological inhibitor on the accumulation of intracellular amyloid beta iAß; hyperphosphorylated protein TAU at Ser202/Thr205; mitochondrial membrane potential (ΔΨm); generation of reactive oxygen species (ROS); oxidized protein DJ-1; proapoptosis proteins p-c-JUN at Ser63/Ser73, TP53, and cleaved caspase 3 (CC3); and deficiency in acetylcholine (ACh)-induced transient Ca2+ influx response in cholinergic-like neurons (ChLNs) bearing the mutation I416T in presenilin 1 (PSEN1 I416T). We found that single doses of TM (50 µM), CU (10 µM), or SP (1 µM) were efficient at reducing some, but not all, pathological markers in PSEN 1 I416T ChLNs, whereas a combination of TM, CU, and SP at a high (50, 10, 1 µM) concentration was efficient in diminishing the iAß, p-TAU Ser202/Thr205, DJ-1Cys106-SO3, and CC3 markers by -50%, -75%, -86%, and -100%, respectively, in PSEN1 I417T ChLNs. Although combinations at middle (10, 2, 0.2) and low (5, 1, 0.1) concentrations significantly diminished p-TAU Ser202/Thr205, DJ-1Cys106-SO3, and CC3 by -69% and -38%, -100% and -62%, -100% and -62%, respectively, these combinations did not alter the iAß compared to untreated mutant ChLNs. Moreover, a combination of reagents at H concentration was able to restore the dysfunctional ACh-induced Ca2+ influx response in PSEN 1 I416T. Our data suggest that the use of multitarget agents in combination with anti-amyloid (TM, CU), antioxidant (e.g., CU), and antiapoptotic (TM, CU, SP) actions might be beneficial for reducing iAß-induced ChLN damage in FAD.

Recent Advances in the Nutrition and Metabolism of Dogs and Cats.

Domestic dogs (facultative carnivores) and cats (obligate carnivores) have been human companions for at least 12,000 and 9000 years, respectively. These animal species have a relatively short digestive tract but a large stomach volume and share many common features of physiological processes, intestinal microbes, and nutrient metabolism. The taste buds of the canine and feline tongues can distinguish sour, umami, bitter, and salty substances. Dogs, but not cats, possess sweet receptors. α-Amylase activity is either absent or very low in canine and feline saliva, and is present at low or substantial levels in the pancreatic secretions of cats or dogs, respectively. Thus, unlike cats, dogs have adapted to high-starch rations while also consuming animal-sourced foods. At metabolic levels, both dogs and cats synthesize de novo vitamin C and many amino acids (AAs, such as Ala, Asn, Asp, Glu, Gln, Gly, Pro, and Ser) but have a very limited ability to form vitamin D3. Compared with dogs, cats have higher requirements for AAs, some B-complex vitamins, and choline; greater rates of gluconeogenesis; a higher capacity to tolerate AA imbalances and antagonism; a more limited ability to synthesize arginine and taurine from glutamine/proline and cysteine, respectively; and a very limited ability to generate polyunsaturated fatty acids (PUFAs) from respective substrates. Unlike dogs, cats cannot convert either ß-carotene into vitamin A or tryptophan into niacin. Dogs can thrive on one large meal daily and select high-fat over low-fat diets, whereas cats eat more frequently during light and dark periods and select high-protein over low-protein diets. There are increasing concerns over the health of skin, hair, bone, and joints (specialized connective tissues containing large amounts of collagen and/or keratin); sarcopenia (age-related losses of skeletal-muscle mass and function); and cognitive function in dogs and cats. Sufficient intakes of proteinogenic AAs and taurine along with vitamins, minerals, and PUFAs are crucial for the normal structures of the skin, hair, bone, and joints, while mitigating sarcopenia and cognitive dysfunction. Although pet owners may have different perceptions about the feeding and management practice of their dogs and cats, the health and well-being of the companion animals critically depend on safe, balanced, and nutritive foods. The new knowledge covered in this volume of Adv Exp Med Biol is essential to guide the formulation of pet foods to improve the growth, development, brain function, reproduction, lactation, and health of the companion animals.

Characteristics of Nutrition and Metabolism in Dogs and Cats.

Domestic dogs and cats have evolved differentially in some aspects of nutrition, metabolism, chemical sensing, and feeding behavior. The dogs have adapted to omnivorous diets containing taurine-abundant meat and starch-rich plant ingredients. By contrast, domestic cats must consume animal-sourced foods for survival, growth, and development. Both dogs and cats synthesize vitamin C and many amino acids (AAs, such as alanine, asparagine, aspartate, glutamate, glutamine, glycine, proline, and serine), but have a limited ability to form de novo arginine and vitamin D3. Compared with dogs, cats have greater endogenous nitrogen losses and higher dietary requirements for AAs (particularly arginine, taurine, and tyrosine), B-complex vitamins (niacin, thiamin, folate, and biotin), and choline; exhibit greater rates of gluconeogenesis; are less sensitive to AA imbalances and antagonism; are more capable of concentrating urine through renal reabsorption of water; and cannot tolerate high levels of dietary starch due to limited pancreatic α-amylase activity. In addition, dogs can form sufficient taurine from cysteine (for most breeds); arachidonic acid from linoleic acid; eicosapentaenoic acid and docosahexaenoic acid from α-linolenic acid; all-trans-retinol from ß-carotene; and niacin from tryptophan. These synthetic pathways, however, are either absent or limited in all cats due to (a) no or low activities of key enzymes (including pyrroline-5-carboxylate synthase, cysteine dioxygenase, ∆6-desaturase, ß-carotene dioxygenase, and quinolinate phosphoribosyltransferase) and (b) diversion of intermediates to other metabolic pathways. Dogs can thrive on one large meal daily, select high-fat over low-fat diets, and consume sweet substances. By contrast, cats eat more frequently during light and dark periods, select high-protein over low-protein diets, refuse dry food, enjoy a consistent diet, and cannot taste sweetness. This knowledge guides the feeding and care of dogs and cats, as well as the manufacturing of their foods. As abundant sources of essential nutrients, animal-derived foodstuffs play important roles in optimizing the growth, development, and health of the companion animals.

Functions and Metabolism of Amino Acids in the Hair and Skin of Dogs and Cats.

The hair and skin of domestic cats or dogs account for 2% and 12-24% of their body weight, respectively, depending on breed and age. These connective tissues contain protein as the major constituent and provide the first line of defense against external pathogens and toxins. Maintenance of the skin and hair in smooth and elastic states requires special nutritional support, particularly an adequate provision of amino acids (AAs). Keratin (rich in cysteine, serine and glycine) is the major protein both in the epidermis of the skin and in the hair. Filaggrin [rich in some AAs (e.g., serine, glutamate, glutamine, glycine, arginine, and histidine)] is another physiologically important protein in the epidermis of the skin. Collagen and elastin (rich in glycine and proline plus 4-hydroxyproline) are the predominant proteins in the dermis and hypodermis of the skin. Taurine and 4-hydroxyproline are abundant free AAs in the skin of dogs and cats, and 4-hydroxyproline is also an abundant free AA in their hair. The epidermis of the skin synthesizes melanin (the pigment in the skin and hair) from tyrosine and produces trans-urocanate from histidine. Qualitative requirements for proteinogenic AAs are similar between cats and dogs but not identical. Both animal species require the same AAs to nourish the hair and skin but the amounts differ. Other factors (e.g., breeds, coat color, and age) may affect the requirements of cats or dogs for nutrients. The development of a healthy coat, especially a black coat, as well as healthy skin critically depends on AAs [particularly arginine, glycine, histidine, proline, 4-hydroxyproline, and serine, sulfur AAs (methionine, cysteine, and taurine), phenylalanine, and tyrosine] and creatine. Although there are a myriad of studies on AA nutrition in cats and dogs, there is still much to learn about how each AA affects the growth, development and maintenance of the hair and skin. Animal-sourced foodstuffs (e.g., feather meal and poultry by-product meal) are excellent sources of the AAs that are crucial to maintain the normal structure and health of the skin and hair in dogs and cats.

Roles of Nutrients in the Brain Development, Cognitive Function, and Mood of Dogs and Cats.

The brain is the central commander of all physical activities and the expression of emotions in animals. Its development and cognitive health critically depend on the neural network that consists of neurons, glial cells (namely, non-neuronal cells), and neurotransmitters (communicators between neurons). The latter include proteinogenic amino acids (e.g., L-glutamate, L-aspartate, and glycine) and their metabolites [e.g., γ-aminobutyrate, D-aspartate, D-serine, nitric oxide, carbon monoxide, hydrogen sulfide, and monoamines (e.g., dopamine, norepinephrine, epinephrine, and serotonin)]. In addition, some non-neurotransmitter metabolites of amino acids, such as taurine, creatine, and carnosine, also play important roles in brain development, cognitive health, behavior, and mood of dogs and cats. Much evidence shows that cats require dietary ω3 (α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid) and ω6 (linoleic acid and arachidonic acid) polyunsaturated fatty acids for the development of the central nervous system. As an essential component of membranes of neurons and glial cells, cholesterol is also crucial for cognitive development and function. In addition, vitamins and minerals are required for the metabolism of AAs, lipids, and glucose in the nervous system, and also act as antioxidants. Thus, inadequate nutrition will lead to mood disorders. Some amino acids (e.g., arginine, glycine, methionine, serine, taurine, tryptophan, and tyrosine) can help to alleviate behavioral and mood disorders (e.g., depression, anxiety and aggression). As abundant providers of all these functional amino acids and lipids, animal-sourced foods (e.g., liver, intestinal mucosa, and meat) play important roles in brain development, cognitive function, and mood of dogs and cats. This may explain, in part, why dogs and cats prefer to eat visceral organs of their prey. Adequate provision of nutrients in all phases of the life cycle (pregnancy, lactation, postnatal growth, and adulthood) is essential for optimizing neurological health, while preventing cognitive dysfunction and abnormal behavior.

Taurine activates the AKT-mTOR axis to restore muscle mass and contractile strength in human 3D in vitro models of steroid myopathy.

Steroid myopathy is a clinically challenging condition exacerbated by prolonged corticosteroid use or adrenal tumors. In this study, we engineered a functional three-dimensional (3D) in vitro skeletal muscle model to investigate steroid myopathy. By subjecting our bioengineered muscle tissues to dexamethasone treatment, we reproduced the molecular and functional aspects of this disease. Dexamethasone caused a substantial reduction in muscle force, myotube diameter and induced fatigue. We observed nuclear translocation of the glucocorticoid receptor (GCR) and activation of the ubiquitin-proteasome system within our model, suggesting their coordinated role in muscle atrophy. We then examined the therapeutic potential of taurine in our 3D model for steroid myopathy. Our findings revealed an upregulation of phosphorylated AKT by taurine, effectively countering the hyperactivation of the ubiquitin-proteasomal pathway. Importantly, we demonstrate that discontinuing corticosteroid treatment was insufficient to restore muscle mass and function. Taurine treatment, when administered concurrently with corticosteroids, notably enhanced contractile strength and protein turnover by upregulating the AKT-mTOR axis. Our model not only identifies a promising therapeutic target, but also suggests combinatorial treatment that may benefit individuals undergoing corticosteroid treatment or those diagnosed with adrenal tumors.

Genetically predicted hypotaurine levels mediate the relationship between immune cells and intracerebral hemorrhage.

The evidence supports a strong link between immune cells and intracerebral hemorrhage (ICH). Nonetheless, the specific cause-and-effect associations between immune cells and ICH remain indeterminate. Here, our primary investigation compared immune cell infiltration in the ICH and sham groups using the GSE24265 dataset. Afterward, we extensively examined the relationship between immune cells and ICH by applying a two-sample Mendelian randomization (MR) analysis to identify the particular immune cells that may be associated with the initiation and advancement of ICH. Nevertheless, the specific processes that regulate the cause-and-effect connection between immune cells and ICH remain unknown. In this study, our objective was to investigate the connections between immune cell characteristics and plasma metabolites, as well as the links between plasma components and ICH. Our investigation uncovered that the levels of hypotaurine play a key role in the advancement of ICH, influencing the ratio of switched memory B cells among lymphocytes. Thus, our findings provide novel insights into the potential biological mechanisms underlying immune cell-mediated ICH.

Taurine amino acid supplementation impacts performance, blood hematology, oxidative stress, and jejunum morphology in broiler chickens.

Excess levels of free radicals cause oxidative damage to cells. Taurine is a rare amino acid with antioxidant effects whose dietary deficiency increases oxidative damage to the cell membrane. To investigate the effects of dietary taurine supplementation on performance, blood hematology, oxidative stress, and jejunum morphology in broilers, 300 broilers (Ras 308, 1D of age) were randomly allocated into 4 groups with 5 replicates of 15 birds. The experimental treatments included basic diet (control treatment) and basic diet with 1, 3, and 6 g/kg taurine amino acid. During 1 to 45 days, the inclusion of taurine supplementation in diets improved the body weight gain (BWG), feed consumption (FC), and feed conversion ratio (FCR) of broilers (P < 0.05). In CBC tests, the experimental treatments were significantly different concerning the red blood cell (RBC) count, the average hemoglobin in the cell, the RBC width in the curve, and the hematocrit (P < 0.05). Despite the significance of oxidative stress among the treatments, the control and fourth treatments showed the highest and the lowest oxidative stress, respectively (P < 0.05). Also, in jejunum morphology, the fourth treatment showed the best performance in terms of villus length and width and the villus length to crypt depth (V/C) ratio (P < 0.05). Overall, 6 g/kg taurine addition to the diet reduced oxidative stress and positive features in the jejunum morphology while improving the functional traits of broilers.

Catheter salvage or removal in catheter-related bloodstream infections with Staphylococcus aureus in children with chronic intestinal failure receiving home parenteral nutrition and the use of prophylactic taurolidine catheter lock solution: A descriptive cohort study.

BACKGROUND: Children with chronic IF require long-term home parenteral nutrition (HPN), administered through a central venous catheter. Catheter-related bloodstream infection (CRBSI) with Staphylococcus aureus is known to be a serious infection with a high mortality rate and risk of complications. A standardized protocol on the management of S aureus CRBSIs in children receiving HPN is lacking. The aim of this study is to evaluate the effectiveness and safety of the current management in an HPN expertise center in the Netherlands. METHODS: We performed a retrospective descriptive cohort study between 2013 and 2022 on children 0-18 years of age with chronic IF requiring long-term HPN. Our primary outcomes were the incidence of S aureus CRBSI per 1000 catheter days, catheter salvage attempt rate, and successful catheter salvage rate. Our secondary outcomes included complications and mortality. RESULTS: A total of 74 patients (39 male; 53%) were included, covering 327.8 catheter years. Twenty-eight patients (38%) had a total of 52 S aureus CRBSIs, with an incidence rate of 0.4 per 1000 catheter days. The catheter salvage attempt rate was 44% (23/52). The successful catheter salvage rate was 100%. No relapse occurred, and no removal was needed after catheter salvage. All complications that occurred were already present at admission before the decision to remove the catheter or not. No patients died because of an S aureus CRBSI. CONCLUSION: Catheter salvage in S aureus CRBSIs in children receiving HPN can be attempted after careful consideration by a multidisciplinary team in an HPN expertise center.

Cancer SLC6A6-mediated taurine uptake transactivates immune checkpoint genes and induces exhaustion in CD8+ T cells.

Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression. Mechanistically, taurine deficiency in CD8+ T cells increases ER stress, promoting ATF4 transcription in a PERK-JAK1-STAT3 signaling-dependent manner. Increased ATF4 transactivates multiple immune checkpoint genes and induces T cell exhaustion. In gastric cancer, we identify a chemotherapy-induced SP1-SLC6A6 regulatory axis. Our findings suggest that tumoral-SLC6A6-mediated taurine deficiency promotes immune evasion and that taurine supplementation reinvigorates exhausted CD8+ T cells and increases the efficacy of cancer therapies.